NT-proBNP Mediates the Association Between FGF23 and All-Cause Mortality in Individuals With Type 2 Diabetes

Amarens van der Vaart; Stephan J L Bakker; Gozewijn D Laverman; Peter R van Dijk; Martin H de Borst

doi:10.1161/JAHA.123.031873

NT-proBNP Mediates the Association Between FGF23 and All-Cause Mortality in Individuals With Type 2 Diabetes

Amarens van der Vaart^*, Stephan J L Bakker, Gozewijn D Laverman, Peter R van Dijk, Martin H de Borst

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

BACKGROUND: FGF23 (fibroblast growth factor 23) is associated with a higher mortality risk in type 2 diabetes, but the mechanism is unclear. We aimed to study whether NT-proBNP (N-terminal pro-brain natriuretic peptide) mediates the association between FGF23 and mortality.

METHODS AND RESULTS: We analyzed C-terminal FGF23 and NT-proBNP levels in 399 patients with type 2 diabetes. Cox regression analyses were performed, followed by mediation analyses using Structural Equation Modeling. During follow-up of 9.2 [7.6-11.3] years, 117 individuals died. FGF23 was associated with all-cause mortality, independent of potential confounders (fully adjusted hazard ratio [HR], 2.32 [95% CI, 1.21-4.43], P=0.01). The association was lost upon further adjustment for NT-proBNP (HR, 1.84; 95% CI, 0.91-3.73). NT-proBNP accounted for 26% of the mediation effect between FGF23 and all-cause mortality.

CONCLUSIONS: These findings suggest that a higher FGF23 level is associated with increased mortality in individuals with type 2 diabetes through an effect on volume homeostasis.

Original language	English
Article number	e031873
Number of pages	5
Journal	Journal of the American Heart Association
Volume	12
Issue number	23
DOIs	https://doi.org/10.1161/JAHA.123.031873
Publication status	Published - 5-Dec-2023

Keywords

Humans
Diabetes Mellitus, Type 2/diagnosis
Biomarkers
Natriuretic Peptide, Brain
Peptide Fragments
Prognosis

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10.1161/JAHA.123.031873Licence: CC BY-NC-ND

NT‐proBNP Mediates the Association Between FGF23 and All‐Cause Mortality in Individuals With Type 2 DiabetesFinal publisher's version, 533 KBLicence: CC BY-NC-ND

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@article{a1e0c86db57b464d83402150504ca11b,

title = "NT-proBNP Mediates the Association Between FGF23 and All-Cause Mortality in Individuals With Type 2 Diabetes",

abstract = "BACKGROUND: FGF23 (fibroblast growth factor 23) is associated with a higher mortality risk in type 2 diabetes, but the mechanism is unclear. We aimed to study whether NT-proBNP (N-terminal pro-brain natriuretic peptide) mediates the association between FGF23 and mortality.METHODS AND RESULTS: We analyzed C-terminal FGF23 and NT-proBNP levels in 399 patients with type 2 diabetes. Cox regression analyses were performed, followed by mediation analyses using Structural Equation Modeling. During follow-up of 9.2 [7.6-11.3] years, 117 individuals died. FGF23 was associated with all-cause mortality, independent of potential confounders (fully adjusted hazard ratio [HR], 2.32 [95% CI, 1.21-4.43], P=0.01). The association was lost upon further adjustment for NT-proBNP (HR, 1.84; 95% CI, 0.91-3.73). NT-proBNP accounted for 26% of the mediation effect between FGF23 and all-cause mortality. CONCLUSIONS: These findings suggest that a higher FGF23 level is associated with increased mortality in individuals with type 2 diabetes through an effect on volume homeostasis.",

keywords = "Humans, Diabetes Mellitus, Type 2/diagnosis, Biomarkers, Natriuretic Peptide, Brain, Peptide Fragments, Prognosis",

author = "{van der Vaart}, Amarens and Bakker, {Stephan J L} and Laverman, {Gozewijn D} and {van Dijk}, {Peter R} and {de Borst}, {Martin H}",

year = "2023",

month = dec,

day = "5",

doi = "10.1161/JAHA.123.031873",

language = "English",

volume = "12",

journal = "Journal of the American Heart Association",

issn = "2047-9980",

publisher = "Wiley",

number = "23",

}

TY - JOUR

T1 - NT-proBNP Mediates the Association Between FGF23 and All-Cause Mortality in Individuals With Type 2 Diabetes

AU - van der Vaart, Amarens

AU - Bakker, Stephan J L

AU - Laverman, Gozewijn D

AU - van Dijk, Peter R

AU - de Borst, Martin H

PY - 2023/12/5

Y1 - 2023/12/5

N2 - BACKGROUND: FGF23 (fibroblast growth factor 23) is associated with a higher mortality risk in type 2 diabetes, but the mechanism is unclear. We aimed to study whether NT-proBNP (N-terminal pro-brain natriuretic peptide) mediates the association between FGF23 and mortality.METHODS AND RESULTS: We analyzed C-terminal FGF23 and NT-proBNP levels in 399 patients with type 2 diabetes. Cox regression analyses were performed, followed by mediation analyses using Structural Equation Modeling. During follow-up of 9.2 [7.6-11.3] years, 117 individuals died. FGF23 was associated with all-cause mortality, independent of potential confounders (fully adjusted hazard ratio [HR], 2.32 [95% CI, 1.21-4.43], P=0.01). The association was lost upon further adjustment for NT-proBNP (HR, 1.84; 95% CI, 0.91-3.73). NT-proBNP accounted for 26% of the mediation effect between FGF23 and all-cause mortality. CONCLUSIONS: These findings suggest that a higher FGF23 level is associated with increased mortality in individuals with type 2 diabetes through an effect on volume homeostasis.

AB - BACKGROUND: FGF23 (fibroblast growth factor 23) is associated with a higher mortality risk in type 2 diabetes, but the mechanism is unclear. We aimed to study whether NT-proBNP (N-terminal pro-brain natriuretic peptide) mediates the association between FGF23 and mortality.METHODS AND RESULTS: We analyzed C-terminal FGF23 and NT-proBNP levels in 399 patients with type 2 diabetes. Cox regression analyses were performed, followed by mediation analyses using Structural Equation Modeling. During follow-up of 9.2 [7.6-11.3] years, 117 individuals died. FGF23 was associated with all-cause mortality, independent of potential confounders (fully adjusted hazard ratio [HR], 2.32 [95% CI, 1.21-4.43], P=0.01). The association was lost upon further adjustment for NT-proBNP (HR, 1.84; 95% CI, 0.91-3.73). NT-proBNP accounted for 26% of the mediation effect between FGF23 and all-cause mortality. CONCLUSIONS: These findings suggest that a higher FGF23 level is associated with increased mortality in individuals with type 2 diabetes through an effect on volume homeostasis.

KW - Humans

KW - Diabetes Mellitus, Type 2/diagnosis

KW - Biomarkers

KW - Natriuretic Peptide, Brain

KW - Peptide Fragments

KW - Prognosis

U2 - 10.1161/JAHA.123.031873

DO - 10.1161/JAHA.123.031873

M3 - Article

C2 - 38014662

SN - 2047-9980

VL - 12

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

IS - 23

M1 - e031873

ER -

NT-proBNP Mediates the Association Between FGF23 and All-Cause Mortality in Individuals With Type 2 Diabetes

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